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Biomedical subjects

K Ishiguro

Publications and source records attributed to K Ishiguro.

At least 163 records · Page 9Linked to original sources
PubMed1991

Alpha 1-antichymotrypsin is present in diffuse senile plaques. A comparative study of beta-protein and alpha 1-antichymotrypsin immunostaining in the Alzheimer brain.

Immunocytochemical examinations of the brains of patients with senile dementia of the Alzheimer type, Down's syndrome, and Gerstmann-Sträusslar-Scheinker disease were performed to clarify the relationship between alpha 1-antichymotrypsin and senile plaque amyloids. Alpha 1-antichymotrypsinlike immunoreactivity was enhanced by protease digestion but not by formic acid pretreatment. Almost all of the diffuse plaques and some small amyloid deposits, which were widely distributed in the cerebral cortex and/or subcortical regions of SDAT brains, were labeled by alpha 1-antichymotrypsin immunostaining. All types of senile plaques, eosinophilic tangles, and some neurons and astrocytes were labeled by alpha 1-antichymotrypsin staining. Diffuse plaques in a Down's syndrome frontal lobe and in a senile dementia of the Alzheimer type cerebellum also were labeled by alpha 1-antichymotrypsin immunostaining. However neither subpial amyloid deposits nor subcortical small amyloid deposits could be detected by alpha 1-antichymotrypsin immunostaining. Kuru plaques in a Gerstmann-Sträusslar-Scheinker disease cerebellum also were not labeled by alpha 1-antichymotrypsin immunostaining. These results suggest that alpha 1-antichymotrypsin is associated with the early to late stages of amyloid deposition and senile plaque formation in senile demential of the Alzheimer type.

Aged↗
PubMed1990

Amyloid beta/A4 protein precursor is bound to neurofibrillary tangles in Alzheimer-type dementia.

Localization of amyloid beta/A4 protein precursor (APP) in Alzheimer's neurofibrillary tangles (NFT) was examined immunohistochemically. Antiserum directed to N-terminal of APP intensely labeled intracellular NFT and some neuropil threads. The NFT, extracted from Alzheimer brains by detergent treatments, were also immunoreactive with this antiserum. Antisera to other parts of APP labeled NFT after the formic acid pretreatment. However, Western blot analysis of NFT demonstrated no immunoreactive bands with APP antiserum. These findings suggest that APP is a minor component of the NFT.

Adult↗
PubMed1990

Alpha 1-antichymotrypsin as a possible biochemical marker for Alzheimer-type dementia.

We measured serum alpha 1-antichymotrypsin levels in 38 patients with Alzheimer-type dementia, 89 control subjects, 2 subjects with Down's syndrome, 20 with vascular dementia, 18 with Parkinson's disease, 14 with spinocerebellar degeneration, 15 with cerebrovascular disease without dementia, and 14 with Duchenne muscular dystrophy. Cerebrospinal fluid (CSF) levels of alpha 1-antichymotrypsin were also measured in 15 patients with Alzheimer-type dementia, 26 control subjects, 6 with vascular dementia, 7 with cerebrovascular disorder, and 11 with degenerative disorders. In control subjects, there were no age-related changes or sex differences. Serum and CSF levels were significantly and specifically higher in patients with Alzheimer-type dementia than in other subjects (serum, p less than 0.001; CSF, p less than 0.05). Serum levels of alpha 1-antichymotrypsin were significantly elevated in the early stage of Alzheimer-type dementia, whereas there was no definite correlation between serum levels and the degree of dementia. CSF levels of alpha 1-antichymotrypsin tended to parallel the severity of dementia. Serum levels were not correlated with CSF levels. These data indicate that serum and CSF levels of alpha 1-antichymotrypsin might be independently upregulated in Alzheimer-type dementia. We concluded that the measurement of serum levels of alpha 1-antichymotrypsin could be useful as a screening marker for Alzheimer-type dementia. In addition, CSF levels also could be a useful marker for Alzheimer-type dementia, because they might reflect the state of dementia.

Age Factors↗
PubMed1990

[Phosphorylation of tau protein].

In aged human brain and particularly in Alzheimer's disease brain, paired helical filaments (PHFs) accumulate in the neuronal cell. Recently, it has been found that the highly phosphorylated tau protein, one of the microtubule-associated proteins (MAPs), is a component of PHF. The authors attempted to clarify the mechanism underlying the accumulation of PHF from the following two aspects; 1) What is the mechanism of phosphorylation of tau protein? 2) Is the highly phosphorylated tau protein capable of forming PHFs? From rat or bovine microtubule proteins we partially purified and characterized a novel protein kinase that specifically phosphorylated tau and MAP2 among many proteins in the brain extract, and which formed a PHF epitope on the phosphorylated human tau. This enzyme was one of the protein serine/threonine kinases and was independent of known second messengers. The phosphorylation of tau by this enzyme was stimulated by tubulin under the condition of microtubule formation, suggesting that the phosphorylation of tau could occur concomitantly with microtubule formation in the brain. Since this kinase was usually bound to tau but not directly to tubulin, the enzyme was associated with microtubules through tau. From these properties related to tau, this kinase is designated as tau protein kinase. The tau that been phosphorylated with this kinase using [gamma-32P]ATP as a phosphate donor, was digested by endoprotinase Lys-C to produce three labeled fragments, K1, K2 and K3. These three fragments were sequenced and the phosphorylation sites on tau by this kinase were identified. The K2 fragment overlapped with the tau-1 site known to be one of the phosphorylation site in PHF. This result strengthens the possibility that tau protein phosphorylated by tau protein kinase is incorporated into PHF. Tubulin binding sites on tau were located between K1 and K3 fragments, while K2 fragment was located in the neighboring to N-terminus of K1. No phosphorylated sites were found on the tubulin-binding domain of tau, leading us to the idea that the interaction of tau with tubulin could induce conformational changes on tau making it accessible to effects of the kinase. We detected -SP- as a sequence common to three major phosphorylation sites on K1, K2 and K3 fragments. Neurofilament-specific kinase and growth-associated histone H1 kinase are known to recognize the consensus sequence including -SP-. These enzymes exhibit certain properties similar to tau protein kinase and seem to play a crucial role in the regulation of neurite outgrowth or cell growth, through the phosphorylation of a specific substrate, neurofilaments or histone H1, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗
PubMed1990

[A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer].

Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with HpO before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine+ was to be given the mouse after X-ray irradiation. The growth of the tumor irradiated with HpO and/or caffeine was more inhibited and the necrotic area was more expanded than that of the tumor irradiated X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the tumor cells irradiated with HpO than that irradiated only. And, the repair of the damaged DNA was more delayed in the tumor cells irradiated with HpO and caffeine than that irradiated with the other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation with HpO and caffeine is useful for clinical treatment of human malignant tumor.

Animals↗
PubMed1990

[Clinical evaluation of vasopressin in the elimination of intestinal gas].

Vasopressin, a hormone secreted from the posterior lobe of the hypophysis, has endocrinological and antidiuretic effects; it contracts vessels and smooth muscles, especially intestinal smooth muscle. In the present study, we investigated the role of vasopressin (Pitressin: arginine-vasopressin) in elimination of intestinal gas on excretory urography reading. Sixty outpatients were randomly divided into six groups. In Group I, the routine procedure was employed, i.e. laxatives the previous night and NPO the morning of the examination. In Groups II to VI, different dose regimens were employed: 6 or 10 units of Pitressin was administered by subcutaneous injection 30 minutes prior to injection of a contrast medium, with or without NPO. Intestinal gas elimination was evaluated by X-ray films taken before and after injection of Pitressin. The efficacy was rated by four grades. There were no significant differences in the gas elimination or occurrence of side effects between any two groups. Younger patients seemed to respond quickly to Pitressin and good effects were obtained. These results indicate that the pretreatment for excretory urography with 6 units of Pitressin without NPO may be a safe and effective alternative method for elimination of intestinal gas, in particular for young patients.

Adolescent↗
PubMed1989

Regulation of transferrin receptor in myeloid and monocytic differentiation of HL-60 leukemia cells.

Modulation of surface transferrin receptor activity has been associated with leukemia cell differentiation and proliferation. To examine the mechanisms involved in regulating this event, receptor protein and mRNA levels were measured in HL-60 promyelocytic leukemia cells induced to differentiate along the myelocytic and monocytic pathways. Transferrin receptor down-regulation which occurs during granulocytic differentiation by dimethyl sulfoxide, retinoic acid, or aclacinomycin A appears to be kinetically compatible with reduced biosynthesis resulting from reductions in the level of steady-state mRNA. In contrast, genetic modulation does not appear to mediate the initial receptor down-regulation seen during 12-O-tetradecanoylphorbol-13-acetate-induced monocytic differentiation. However, a reduction in levels of receptor message appears to contribute to the maintenance of diminished transferrin receptor activity in these 12-O-tetradecanoylphorbol-13-acetate-treated cells. A common feature of myelocytic and monocytic differentiating cells is the complete inhibition of cellular proliferation observed within 10 to 16 h following a four-fold reduction in surface transferrin receptor. We conclude that the early decline in transferrin receptor levels precludes its regulation as a consequence of the decrease in proliferation, but rather implicates its role in the programmed cessation of growth which is requisite for the terminal differentiation of these cells.

Aclarubicin↗
PubMed1989

[Guideline of surgical treatment of prostatic adenocarcinoma].

Based on study of 274 cases of prostate cancer treated in our clinic, selection of patient for radical surgical treatment and choice of procedures were discussed. The radical surgical procedures experienced in our clinic were classified as 31 cases of radical prostatectomy, 4 cases of radical cystoprostatectomy and 7 cases of pelvic exenteration. The endocrine therapy was added to non curative cases postoperatively. In the radical prostatectomy group, the 5-year survival rate of patients with stage A and stage B prostatic adenocarcinoma were 100 and 93 per cent, respectively, and 5-year survival rate of patients who had stage C prostatic adenocarcinoma was 75 per cent. The 5-year survival rates of patients with stage C prostatic adenocarcinoma treated by radical cystoprostatectomy and pelvic exenteration were 50 per cent and 66 per cent, respectively. Cancer recurrence has not seen in the bladder in the patients with stage C prostatic adenocarcinoma treated by radical prostatectomy. Operation of urinary diversion had improved the quality of life. From this data, radical prostatectomy would be indicated for the treatment of patients with stage A, stage B and stage C prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1989

[A case of mitochondrial encephalomyopathy characterized by repeated stroke-like episodes].

We reported a case of mitochondrial encephalomyopathy with repeated stroke-like episodes. A 33-year-old single male was admitted to our hospital because of stroke-like episodes with visual field defect, hemiplegia and convulsion repeated seven times for the past seven years. There were no abnormalities on the physical examination. He was hallucinative and perseverative and had mental deficiency. Muscle weakness and atrophy were not prominent, and generalized hyporeflexia were present without pathological reflexes. Myoclonus was not observed. Serum CK and blood gas analysis were normal (pH 7.398). Although blood levels of lactate and pyruvate were almost within normal limit, lactate was elevated by 20WATT-15 minutes exercises. On the contrary, the CSF levels of lactate and pyruvate were elevated markedly. CT of the brain revealed the presence of the low density areas in the right occipital and the left frontal lobes. Cranial 4 vessels studies were unremarkable. EEG showed the diffuse slowness with spike and wave complex. CT of the muscles were normal. A specimen obtained from the left biceps brachii muscle showed ragged-red fibers without obvious myogenic or neurogenic changes, and accumulations of abnormal mitochondria with paracrystalline inclusion bodies were observed by electron microscopy. However, mitochondrial abnormalities were not seen in the vessel walls in the biopsied muscle. Activities of complex I + III, II + III, IV in mitochondria were normal. Clinical features of this case were consistent with MELAS. However, this case showed no muscle weakness, short stature and lactic acidosis which characterize MELAS, and the onset of this case was later than those cases that were reported before.

Adult↗
PubMed1989

[The significance of measurement of contents of serum serine protease inhibitors in senile dementia of the Alzheimer type].

We have evaluated serum alpha 1-antichymotrypsin content in dementia of the Alzheimer type (DAT). The subjects consisted of 26 patients with DAT, 15 with cerebrovascular dementia, 10 with mixed type dementia, 2 with Down syndrome, 17 with Parkinson disease, 14 with spinocerebellar degeneration, 14 with cerebrovascular disease without dementia, 12 with Duchenne muscular dystrophy and 77 normal controls. DAT group showed statistically significant increase of serum alpha 1-antichymotrypsin content, as compared with normal control group (p less than 0.001), mixed type dementia group (p less than 0.05) and other 6 groups (p less than 0.001). However, the levels of both alpha 1-antitrypsin content and inter-alpha-trypsin inhibitor content, included in serine protease inhibitors, were not significantly different between DAT and normal control groups. These findings indicated that measurement of serum alpha 1-antichymotrypsin is useful as the diagnostic marker of DAT.

Adult↗
PubMed1988

Different immune functions of peripheral blood, regional lymph node, and tumor infiltrating lymphocytes in lung cancer patients.

Immune functions of peripheral blood (PBL), regional lymph node (RLNL), and tumor infiltrating lymphocytes (TIL) were evaluated in lung cancer patients. PBL had many natural killer (NK) cells and the highest NK activity, and it showed the highest augmentation of NK activity by interferon-gamma (IFN-gamma) + recombinant interleukin-2 (rIL-2) among the three groups of lymphocytes. PBL had high lymphokine-activated killer (LAK) activity of against a broad spectrum of cell lines and moderate activity against autologous tumor cells by increased effector to target (ET) ratio but the lowest ability of IL-2 production of the three groups of lymphocytes. The RLNL not associated with tumor metastasis had a few NK cells and lower NK activity than PBL, but its LAK activity was almost the same but not greater than that of PBL. RLNL had the highest ability of IL-2 production among the three groups of lymphocytes. All activities of RLNL associated with tumor metastasis were lower than those not associated with tumor metastasis. TIL exclusively consisted of T-cells, especially cytotoxic/suppressor T-lymphocytes. NK activity and lymphocyte blastogenesis of TIL were lower than those of other groups. The LAK activity of TIL differed greatly with the case, and it was the highest against autologous tumor cells among the three groups of lymphocytes in three of eight cases. These findings showed that PBL, RLNL, and TIL had characteristic subpopulations of lymphocytes and different functions of host immune responses in lung cancer. Efficient augmentation of the characteristic immune responses will lead to a more effective total cancer therapy.

Adult↗
PubMed1988

A novel tubulin-dependent protein kinase forming a paired helical filament epitope on tau.

From rat brain microtubule proteins, we purified a protein kinase that phosphorylated tau, one of microtubule-associated proteins. The electrophoretic mobility of the phosphorylated tau on SDS-polyacrylamide gel decreased. The enzyme was not activated by cyclic nucleotides, calmodulin, or phospholipids, and was inhibited by the calcium ions. The kinase bound to tau. The phosphorylation of tau was stimulated by tubulin under the condition of microtubule formation. From these results we propose an idea that the phosphorylation could occur concomitantly with microtubule formation in the brain. Human tau phosphorylated by the kinase carried an epitope of the paired helical filaments that accumulate in the brain in Alzheimer's disease.

Animals↗
PubMed1988

Studies on iridoid-related compounds. V. Antitumor activity of iridoid dervs. periodate oxidation products.

In the course of a modification study of iridoid glucosides to investigate their antitumor and antimicrobial activity, we found that about all metaperiodate oxidation products of iridoid glucosides which had no antitumor activity showed potent activity against the leukemia P388 in mice. They were found to be more active than the corresponding aglycones obtained by enzymic hydrolysis of iridoid glucosides. Among them, periodate oxidation product of sweroside showed the most potent activity, of which the maximum total/control (T/C) value was 198% at 200 mg/kg.

Animals↗
PubMed1988

[Clinical studies on Suncefal (cefpiramide) concentration in prostatic tissue and bladder wall].

The cefpiramide (CPM) concentration in prostatic tissue of 19 patients with benign prostatic hypertrophy and bladder wall of 2 patients with bladder tumors was measured, after 2 g of CPM was administered intravenously by bolus technique prior to operation. Prostatic tissue level was 28.4 to 131 micrograms/g and tissue to serum ratio 0.15 to 0.63 at 12 min. to 220 min. after administration. The T1/2 of CPM in prostatic tissue was 3.29 hours. The bladder wall level was high at both determinations. CPM level in prostatic tissue and bladder wall covered the minimum inhibitory concentration of many bacteria detected from the infected sites. Therefore, CPM which has a strong antimicrobial activity can be considered as a highly useful antibiotic for the treatment of postoperative infections.

Aged↗